The Early Minimally Invasive Removal of Intracerebral Hemorrhage (ENRICH) trial demonstrated that minimally invasive surgery to treat spontaneous lobar intracerebral hemorrhage (ICH) improved functional outcomes. We aimed to explore current management trends for spontaneous lobar ICH in Canada to assess practice patterns and determine whether further randomized controlled trials are needed to clarify the role of surgical intervention.

Neurologists, neurosurgeons, physiatrists and trainees in these specialties were invited to complete a 16-question survey exploring three areas: (1) current management for spontaneous lobar ICH at their institution, (2) perceived influence of ENRICH on their practice and (3) perceived need for additional clinical trial data. Standard descriptive statistics were used to report categorical variables. The χ2 test was used to compare responses across specialties and career stages.

The survey was sent to 433 physicians, and 101 (23.3%) responded. Sixty-eight percent of participants reported that prior to publication of the ENRICH trial, spontaneous lobar ICH was primarily managed conservatively, with surgery reserved for life-threatening situations. Forty-three percent of participants did not foresee a significant increase in surgical intervention at their institution. Of neurosurgical respondents, 33% remained hesitant to offer surgical intervention beyond lifesaving operations. Only 5% reported routinely using specifically designed technologies to evacuate ICH. Seventy percent reported that another randomized controlled trial comparing nonsurgical to surgical management for spontaneous lobar ICH is needed.

There is significant practice variability in the management of spontaneous lobar ICH across Canadian institutions, stressing the need for additional clinical trial data to determine the role of surgical intervention.

Preliminary evidence suggests that a ketogenic diet may be effective for bipolar disorder.

To assess the impact of a ketogenic diet in bipolar disorder on clinical, metabolic and magnetic resonance spectroscopy outcomes.

Euthymic individuals with bipolar disorder (N = 27) were recruited to a 6- to 8-week single-arm open pilot study of a modified ketogenic diet. Clinical, metabolic and MRS measures were assessed before and after the intervention.

Of 27 recruited participants, 26 began and 20 completed the ketogenic diet. For participants completing the intervention, mean body weight fell by 4.2 kg (P < 0.001), mean body mass index fell by 1.5 kg/m2 (P < 0.001) and mean systolic blood pressure fell by 7.4 mmHg (P < 0.041). The euthymic participants had average baseline and follow-up assessments consistent with them being in the euthymic range with no statistically significant changes in Affective Lability Scale-18, Beck Depression Inventory and Young Mania Rating Scale. In participants providing reliable daily ecological momentary assessment data (n = 14), there was a positive correlation between daily ketone levels and self-rated mood (r = 0.21, P < 0.001) and energy (r = 0.19 P < 0.001), and an inverse correlation between ketone levels and both impulsivity (r = −0.30, P < 0.001) and anxiety (r = −0.19, P < 0.001). From the MRS measurements, brain glutamate plus glutamine concentration decreased by 11.6% in the anterior cingulate cortex (P = 0.025) and fell by 13.6% in the posterior cingulate cortex (P = <0.001).

These findings suggest that a ketogenic diet may be clinically useful in bipolar disorder, for both mental health and metabolic outcomes. Replication and randomised controlled trials are now warranted.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Following a health technology assessment, the Health Service Executive (HSE) supported reimbursement of dupilumab subject to a managed access protocol (MAP) being implemented. Reimbursement is restricted to a subgroup of the fully licensed indication, that is, moderate-to-severe refractory atopic dermatitis (AD) in adults and adolescents 12 years and older. This study provides an overview of the first year of the MAP.

All reimbursement applications submitted to the HSE Medicines Management Programme between 1 April 2021 and 31 March 2022 were reviewed. Key demographic and clinical characteristics of the approved population were analyzed. Reimbursement claims data within the specified period were extracted from the HSE Primary Care Reimbursement Services national pharmacy claims database. All data were compiled and analyzed using SPSS Statistics 27. Expenditure estimates were based on wholesale prices and were exclusive of value-added tax, fees, and confidential rebates.

During the study period, 382 applications were submitted, 96 percent (n=365) of which were approved. Among approved patients, the mean age was 35 years (range 12 to 79 years), the mean number of years between AD diagnosis and approval was 22.65 years (range 1 to 78 years), and 65 percent (n=238) were men. The mean Eczema Area and Severity Index score was 28.72 and the mean (Children’s) Dermatology Life Quality Index score was 19.72. Approved patients who had unsuccessfully tried other systemic immunosuppressants had trialed up to five different medicines (mean=1.6). Year one expenditure was EUR2.4million, with 70 percent of approved patients accessing treatment.

Most applications submitted through the MAP were approved. These patients met the predefined evidence-based eligibility criteria for treatment. Patient numbers were higher than estimated, suggesting that the MAP did not hinder access. Utilizing health technology management by way of a MAP has facilitated access to expensive medicines for patients with the greatest need, while controlling expenditure for the payer.

The calcitonin gene-related peptide monoclonal antibodies (CGRP MABs) erenumab, fremanezumab, and galcanezumab are reimbursed in Ireland under the High Tech Arrangement, subject to a managed access protocol (MAP), for the prophylaxis of chronic migraine in adults in whom three or more prophylactic treatments have failed. This study provides an overview of submitted reimbursement applications and the utilization of CGRP MABs.

The MAP for CGRP MABs was introduced on 1 September 2021 and is operated by the Health Service Executive (HSE) Medicines Management Programme. Individual patient reimbursement applications for CGRP MABs submitted through an online reimbursement application system between 1 September 2021 and 30 April 2023 were reviewed. Utilization data from 1 September 2021 to 30 April 2023 were extracted from the HSE Primary Care Reimbursement Service national pharmacy reimbursement claims database for the High Tech Arrangement. Analysis was performed using SAS® 9.4 software.

A total of 1,517 reimbursement applications were submitted in the study period. Reimbursement was approved for 96.1 percent (n=1,458) of the applications. A total of 1,399 individual patients (mean age 45 years) were dispensed a CGRP MAB under the High Tech Arrangement between September 2021 and April 2023, the majority of whom were women (n=1,141). Almost 90 percent of patients were considered treatment adherent. In April 2023, the market share of the individual CGRP MABs on the High Tech Arrangement was 56 percent (n=599) for fremanezumab, 38.3 percent (n=409) for erenumab, and 5.7 percent (n=61) for galcanezumab.

MAPs are part of the health technology management approach to drug reimbursement in the Irish healthcare setting, ensuring that reimbursement is in line with approved subgroups of the licensed indication. Used in conjunction with health technology assessment, MAPs enable access to high-cost drug treatments for patients with the greatest unmet need, while providing budgetary oversight and certainty for the payer.

Increasingly in Ireland, there are specific criteria attached to reimbursement approval for new medicines. Health technology assessment (HTA) identifies where uncertainty is greatest in relation to clinical and cost-effectiveness evidence and budget impact estimates; our health technology management (HTM) approach uses these outputs from HTA to design protocols to manage these uncertainties in the post-reimbursement phase.

A bespoke managed access protocol (MAP) is developed for each medicine reimbursed under this approach, informed by uncertainties highlighted in the HTA, directions from the decision-maker, and relevant particulars arising from commercial negotiations. Individual patient reimbursement applications are submitted via an online application system linked directly to the national pharmacy claims system. Pharmacists review the applications and approve reimbursement support where the patient meets the reimbursement criteria. The process is adaptive, allowing expansion of the criteria to include previously excluded patient cohorts, and the addition of new indications. It can also work across differing reimbursement arrangements (hospital/primary care).

The MAP for liraglutide for weight management confines reimbursement to patients with a body mass index greater than or equal to 35 kg/m², prediabetes, and high risk for cardiovascular disease. Phase I reimbursement support lasts for six months; patients not attaining greater than or equal to five percent weight loss are deemed non-responders as per the HTA, and reimbursement support is discontinued. The MAP for dupilumab confined reimbursement support to adults with refractory moderate-to-severe atopic dermatitis, where cost-effectiveness was plausible in the HTA. The MAP for calcitonin-gene-related-peptides monoclonal antibodies confines reimbursement support to patients with chronic migraine, refractory to at least three prophylactic treatments, where cost-effectiveness was plausible in the HTA.

Across these MAPs, over 3,000 patients accessed novel treatments for chronic illnesses in September 2023. HTM provides an effective mechanism to facilitate access to high-cost medicines for targeted patient groups, while providing increased oversight and budgetary certainty. Key to acceptance is utilization of HTA outputs to implement evidence-based HTM measures targeting specific uncertainties as highlighted in the HTA report.

Racial and ethnic variations in antibiotic utilization are well-reported in outpatient settings but little is known about inpatient settings. Our objective was to describe national inpatient antibiotic utilization among children by race and ethnicity.

This study included hospital visit data from the Pediatric Health Information System between 01/01/2022 and 12/31/2022 for patients <20 years. Primary outcomes were the percentage of hospitalization encounters that received an antibiotic and antibiotic days of therapy (DOT) per 1000 patient days. Mixed-effect regression models were used to determine the association of race-ethnicity with outcomes, adjusting for covariates.

There were 846,530 hospitalizations. 45.2% of children were Non-Hispanic (NH) White, 27.1% were Hispanic, 19.2% were NH Black, 4.5% were NH Other, 3.5% were NH Asian, 0.3% were NH Native Hawaiian/Other Pacific Islander (NHPI) and 0.2% were NH American Indian. Adjusting for covariates, NH Black children had lower odds of receiving antibiotics compared to NH White children (aOR 0.96, 95%CI 0.94–0.97), while NH NHPI had higher odds of receiving antibiotics (aOR 1.16, 95%CI 1.05–1.29). Children who were Hispanic, NH Asian, NH American Indian, and children who were NH Other received antibiotic DOT compared to NH White children, while NH NHPI children received more antibiotic DOT.

Antibiotic utilization in children’s hospitals differs by race and ethnicity. Hospitals should assess policies and practices that may contribute to disparities in treatment; antibiotic stewardship programs may play an important role in promoting inpatient pharmacoequity. Additional research is needed to examine individual diagnoses, clinical outcomes, and drivers of variation.

Pragmatic trials aim to speed translation to practice by integrating study procedures in routine care settings. This study evaluated implementation outcomes related to clinician and patient recruitment and participation in a trial of community paramedicine (CP) and presents successes and challenges of maintaining pragmatic study features.

Adults in the pre-hospital setting, emergency department (ED), or hospital being considered for referral to the ED/hospital or continued hospitalization for intermediate-level care were randomized 1:1 to CP care or usual care. Referral and enrollment data were tracked administratively, and patient characteristics were abstracted from the electronic health record (EHR). Enrolled patients completed baseline surveys, and a subset of intervention patients were interviewed. All CPs and a sample of clinicians and administrators were invited to complete a survey and interview.

Between January 2022 and February 2023, 240 enrolled patients (42% rural) completed surveys, and 22 completed an interview; 63 staff completed surveys and 20 completed an interview. Ninety-three clinicians in 27 departments made at least one referral. Factors related to referrals included program awareness and understanding the CP practice scope. Most patients were enrolled in the hospital, but characteristics were similar to the primary care population and included older and medically complex patients. Challenges to achieving representativeness included limited EHR infrastructure, constraints related to patient consenting, and clinician concerns about patient randomization disrupting preferred care.

Future pragmatic trials in busy clinical settings may benefit from regulatory policies and EHR capabilities that allow for real-world study conduct and representative participation. Trial registration: NCT05232799.

To understand the relationship between adolescents’ unhealthy snacking behaviour during their school journey and their perceived and objective measures of food outlet availability in the school neighbourhood.

A cross-sectional survey enquired about socio-demographic information, school transport modes, perceived presence of food outlets in the school neighbourhood and unhealthy food purchase and consumption on the school journey. A geographical information system analysis of the food outlets within 500 m and 1000 m school buffers was undertaken. Data were analysed using generalised linear mixed modelling.

All twelve secondary schools in Dunedin, Aotearoa New Zealand, March 2020–June 2022.

Adolescents aged 13–18 years (n 725) who reported being familiar with their school neighbourhood.

Perceived availability of food outlets in the school neighbourhood was inversely correlated with distance to the closest food outlet from school and positively correlated with food outlet density within 500 m and 1000 m school buffers. Adolescents’ purchase and consumption of unhealthy snacks and drinks during the school journey were associated with perceived availability of food outlets and with shorter distance to the closest food outlet from school. Mixed transport users, girls and those living in high-deprivation neighbourhoods had higher odds of purchasing and consuming unhealthy snacks and drinks during the school journey than active transport users, boys and those living in low-deprivation neighbourhoods, respectively.

Adolescents perceptions of the food environment and close access to food outlets in the school neighbourhood may influence adolescents’ food purchase and consumption behaviours during the school journey.